1,040 research outputs found
Cyclosporine pharmakokinetic profiles in liver, heart, and kidney transplant patients as determined HPLC
Generality of shear thickening in suspensions
Suspensions are of wide interest and form the basis for many smart fluids.
For most suspensions, the viscosity decreases with increasing shear rate, i.e.
they shear thin. Few are reported to do the opposite, i.e. shear thicken,
despite the longstanding expectation that shear thickening is a generic type of
suspension behavior. Here we resolve this apparent contradiction. We
demonstrate that shear thickening can be masked by a yield stress and can be
recovered when the yield stress is decreased below a threshold. We show the
generality of this argument and quantify the threshold in rheology experiments
where we control yield stresses arising from a variety of sources, such as
attractions from particle surface interactions, induced dipoles from applied
electric and magnetic fields, as well as confinement of hard particles at high
packing fractions. These findings open up possibilities for the design of smart
suspensions that combine shear thickening with electro- or magnetorheological
response.Comment: 11 pages, 9 figures, accepted for publication in Nature Material
Taxonomy and identification of bacteria associated with acute oak decline
© 2017, The Author(s). Acute oak decline (AOD) is a relatively newly described disorder affecting native oak species in Britain. Symptomatic trees are characterised by stem bleeds from vertical fissures, necrotic lesions in the live tissue beneath and larval galleries of the two spotted oak buprestid (Agrilus biguttatus). Several abiotic and biotic factors can be responsible for tree death, however the tissue necrosis and stem weeping is thought to be caused by a combination of bacterial species. Following investigations of the current episode of AOD which began in 2008, numerous strains belonging to several different bacteria in the family Enterobacteriaceae have been consistently isolated from symptomatic tissue. The majority of these enterobacteria were found to be novel species, subspecies and even genera, which have now been formally classified. The most frequently isolated species from symptomatic oak are Gibbsiella quercinecans, Brenneria goodwinii and Rahnella victoriana. Identification of these bacteria is difficult due to similarities in colony morphology, phenotypic profile and 16S rRNA gene sequences. Current identification relies heavily on gyrB gene amplification and sequencing, which is time consuming and laborious. However, newer techniques based on detection of single nucleotide polymorphisms show greater promise for rapid and reliable identification of the bacteria associated with AOD
Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial
BACKGROUND: Low-grade serous carcinoma of the ovary or peritoneum is characterised by MAPK pathway aberrations and its reduced sensitivity to chemotherapy relative to high-grade serous carcinoma. We compared the MEK inhibitor trametinib to physician's choice standard of care in patients with recurrent low-grade serous carcinoma. METHODS: This international, randomised, open-label, multicentre, phase 2/3 trial was done at 84 hospitals in the USA and UK. Eligible patients were aged 18 years or older with recurrent low-grade serous carcinoma and measurable disease, as defined by Response Evaluation Criteria In Solid Tumors version 1.1, had received at least one platinum-based regimen, but not all five standard-of-care drugs, and had received an unlimited number of previous regimens. Patients with serous borderline tumours or tumours containing low-grade serous and high-grade serous carcinoma were excluded. Eligible patients were randomly assigned (1:1) to receive either oral trametinib 2 mg once daily (trametinib group) or one of five standard-of-care treatment options (standard-of-care group): intravenous paclitaxel 80 mg/m2 by body surface area on days 1, 8, and 15 of every 28-day cycle; intravenous pegylated liposomal doxorubicin 40-50 mg/m2 by body surface area once every 4 weeks; intravenous topotecan 4 mg/m2 by body surface area on days 1, 8, and 15 of every 28-day cycle; oral letrozole 2·5 mg once daily; or oral tamoxifen 20 mg twice daily. Randomisation was stratified by geographical region (USA or UK), number of previous regimens (1, 2, or ≥3), performance status (0 or 1), and planned standard-of-care regimen. The primary endpoint was investigator-assessed progression-free survival while receiving randomised therapy, as assessed by imaging at baseline, once every 8 weeks for 15 months, and then once every 3 months thereafter, in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study therapy. This trial is registered with ClinicalTrials.gov, NCT02101788, and is active but not recruiting. FINDINGS: Between Feb 27, 2014, and April 10, 2018, 260 patients were enrolled and randomly assigned to the trametinib group (n=130) or the standard-of-care group (n=130). At the primary analysis, there were 217 progression-free survival events (101 [78%] in the trametinib group and 116 [89%] in the standard-of-care group). Median progression-free survival in the trametinib group was 13·0 months (95% CI 9·9-15·0) compared with 7·2 months (5·6-9·9) in the standard-of-care group (hazard ratio 0·48 [95% CI 0·36-0·64]; p<0·0001). The most frequent grade 3 or 4 adverse events in the trametinib group were skin rash (17 [13%] of 128), anaemia (16 [13%]), hypertension (15 [12%]), diarrhoea (13 [10%]), nausea (12 [9%]), and fatigue (ten [8%]). The most frequent grade 3 or 4 adverse events in the standard-of-care group were abdominal pain (22 [17%]), nausea (14 [11%]), anaemia (12 [10%]), and vomiting (ten [8%]). There were no treatment-related deaths. INTERPRETATION: Trametinib represents a new standard-of-care option for patients with recurrent low-grade serous carcinoma. FUNDING: NRG Oncology, Cancer Research UK, Target Ovarian Cancer, and Novartis
International criteria for acute kidney injury: advantages and remaining challenges
• Acute Kidney Injury (AKI) is defined using widely accepted international criteria that are based on changes in serum creatinine concentration and degree of oliguria.
• AKI, when defined in this way, has a strong association with poor patient outcomes, including high mortality rates and longer hospital admissions with increased resource utilisation and subsequent chronic kidney disease.
• The detection of AKI using current criteria can assist with AKI diagnosis and stratification of individual patient risk.
• The diagnosis of AKI requires clinical judgement to integrate the definition of AKI with the clinical situation, to determine underlying cause of AKI, and to take account of factors that may affect performance of current definitions
Searches for Gravitational Waves from Binary Neutron Stars: A Review
A new generation of observatories is looking for gravitational waves. These
waves, emitted by highly relativistic systems, will open a new window for ob-
servation of the cosmos when they are detected. Among the most promising
sources of gravitational waves for these observatories are compact binaries in
the final min- utes before coalescence. In this article, we review in brief
interferometric searches for gravitational waves emitted by neutron star
binaries, including the theory, instru- mentation and methods. No detections
have been made to date. However, the best direct observational limits on
coalescence rates have been set, and instrumentation and analysis methods
continue to be refined toward the ultimate goal of defining the new field of
gravitational wave astronomy.Comment: 30 pages, 5 Figures, to appear in "Short-Period Binary Stars:
Observations, Analyses, and Results", Ed.s Eugene F. Milone, Denis A. Leahy,
David W. Hobil
The Saccadic and Neurological Deficits in Type 3 Gaucher Disease
Our objective was to characterize the saccadic eye movements in patients with type 3 Gaucher disease (chronic neuronopathic) in relationship to neurological and neurophysiological abnormalities. For approximately 4 years, we prospectively followed a cohort of 15 patients with Gaucher type 3, ages 8–28 years, by measuring saccadic eye movements using the scleral search coil method. We found that patients with type 3 Gaucher disease had a significantly higher regression slope of duration vs amplitude and peak duration vs amplitude compared to healthy controls for both horizontal and vertical saccades. Saccadic latency was significantly increased for horizontal saccades only. Downward saccades were more affected than upward saccades. Saccade abnormalities increased over time in some patients reflecting the slowly progressive nature of the disease. Phase plane plots showed individually characteristic patterns of abnormal saccade trajectories. Oculo-manual dexterity scores on the Purdue Pegboard test were low in virtually all patients, even in those with normal cognitive function. Vertical saccade peak duration vs amplitude slope significantly correlated with IQ and with the performance on the Purdue Pegboard but not with the brainstem and somatosensory evoked potentials. We conclude that, in patients with Gaucher disease type 3, saccadic eye movements and oculo-manual dexterity are representative neurological functions for longitudinal studies and can probably be used as endpoints for therapeutic clinical trials
Characteristic Evolution and Matching
I review the development of numerical evolution codes for general relativity
based upon the characteristic initial value problem. Progress in characteristic
evolution is traced from the early stage of 1D feasibility studies to 2D
axisymmetric codes that accurately simulate the oscillations and gravitational
collapse of relativistic stars and to current 3D codes that provide pieces of a
binary black hole spacetime. Cauchy codes have now been successful at
simulating all aspects of the binary black hole problem inside an artificially
constructed outer boundary. A prime application of characteristic evolution is
to extend such simulations to null infinity where the waveform from the binary
inspiral and merger can be unambiguously computed. This has now been
accomplished by Cauchy-characteristic extraction, where data for the
characteristic evolution is supplied by Cauchy data on an extraction worldtube
inside the artificial outer boundary. The ultimate application of
characteristic evolution is to eliminate the role of this outer boundary by
constructing a global solution via Cauchy-characteristic matching. Progress in
this direction is discussed.Comment: New version to appear in Living Reviews 2012. arXiv admin note:
updated version of arXiv:gr-qc/050809
The burden of neglected tropical diseases in Ethiopia, and opportunities for integrated control and elimination
Background:
Neglected tropical diseases (NTDs) are a group of chronic parasitic diseases and related conditions that are the most common diseases among the 2·7 billion people globally living on less than US$2 per day. In response to the growing challenge of NTDs, Ethiopia is preparing to launch a NTD Master Plan. The purpose of this review is to underscore the burden of NTDs in Ethiopia, highlight the state of current interventions, and suggest ways forward.
Results:
This review indicates that NTDs are significant public health problems in Ethiopia. From the analysis reported here, Ethiopia stands out for having the largest number of NTD cases following Nigeria and the Democratic Republic of Congo. Ethiopia is estimated to have the highest burden of trachoma, podoconiosis and cutaneous leishmaniasis in sub-Saharan Africa (SSA), the second highest burden in terms of ascariasis, leprosy and visceral leishmaniasis, and the third highest burden of hookworm. Infections such as schistosomiasis, trichuriasis, lymphatic filariasis and rabies are also common. A third of Ethiopians are infected with ascariasis, one quarter is infected with trichuriasis and one in eight Ethiopians lives with hookworm or is infected with trachoma. However, despite these high burdens of infection, the control of most NTDs in Ethiopia is in its infancy. In terms of NTD control achievements, Ethiopia reached the leprosy elimination target of 1 case/10,000 population in 1999. No cases of human African trypanosomiasis have been reported since 1984. Guinea worm eradication is in its final phase. The Onchocerciasis Control Program has been making steady progress since 2001. A national blindness survey was conducted in 2006 and the trachoma program has kicked off in some regions. Lymphatic Filariasis, podoconiosis and rabies mapping are underway.
Conclusion:
Ethiopia bears a significant burden of NTDs compared to other SSA countries. To achieve success in integrated control of NTDs, integrated mapping, rapid scale up of interventions and operational research into co implementation of intervention packages will be crucial
Development of mental health first aid guidelines for Aboriginal and Torres Strait Islander people experiencing problems with substance use: a Delphi study
<p>Abstract</p> <p>Background</p> <p>Problems with substance use are common in some Aboriginal communities. Although problems with substance use are associated with significant mortality and morbidity, many people who experience them do not seek help. Training in mental health first aid has been shown to be effective in increasing knowledge of symptoms and behaviours associated with seeking help. The current study aimed to develop culturally appropriate guidelines for providing mental health first aid to an Aboriginal or Torres Strait Islander person who is experiencing problem drinking or problem drug use (e.g. abuse or dependence).</p> <p>Methods</p> <p>Twenty-eight Aboriginal health experts participated in two independent Delphi studies (n = 22 problem drinking study, n = 21 problem drug use; 15 participated in both). Panellists were presented with statements about possible first aid actions via online questionnaires and were encouraged to suggest additional actions not covered by the content. Statements were accepted for inclusion in the guidelines if they were endorsed by ≥ 90% of panellists as either 'Essential' or 'Important'. At the end of the two Delphi studies, participants were asked to give feedback on the value of the project and their participation experience.</p> <p>Results</p> <p>From a total of 735 statements presented over two studies, 429 were endorsed (223 problem drinking, 206 problem drug use). Statements were grouped into sections based on common themes (n = 7 problem drinking, n = 8 problem drug use), then written into guideline documents. Participants evaluated the Delphi method employed, and the guidelines developed, as useful and appropriate for Aboriginal and Torres Strait Islander people.</p> <p>Conclusions</p> <p>Aboriginal health experts were able to reach consensus about culturally appropriate first aid for problems with substance use. Many first aid actions endorsed in the current studies were not endorsed in previous international Delphi studies, conducted on problem drinking and problem drug use in non-Indigenous people, highlighting the need for culturally specific first aid strategies to be employed when assisting Aboriginal or Torres Strait Islander people.</p
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